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In Silico Studies and In Vivo MAOA Inhibitory Activity of Coumarins Isolated from Angelica archangelica Extract: An Approach toward Antidepressant Activity.

ABSTRACT: The current investigation was aimed at in vivo MAOA inhibitory activity of coumarins angelicin, bergapten, and scopoletin isolated from the roots of Angelica archangelica. The isolated compounds were screened for MAOA (pdb ID 2Z5y) binding through molecular docking studies. The molecular docking results displayed that bergapten has a maximum affinity for MAOA, followed by angelicin and scopoletin. In silico prediction of physicochemical parameters indicated that maximum blood-brain barrier (BBB) permeability was observed with angelicin (2.3), followed by bergapten (2.0) and least with scopoletin (0.644). In consonance to the results of molecular docking studies, appreciable in vivo antidepressant activity of angelicin and bergaptan was observed over the mouse model of reserpine-induced depression. The modulation of MAOA in the antidepressant effect of extract and its isolated fractions was also determined. Biochemical examination of the brain tissue indicated that bergapten has maximum MAOA inhibitory activity while scopoletin fails to inhibit brain MAOA.

SUBMITTER: Kaur A

PROVIDER: S-EPMC7330908 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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In Silico Studies and In Vivo MAOA Inhibitory Activity of Coumarins Isolated from Angelica archangelica Extract: An Approach toward Antidepressant Activity.

Kaur Anudeep A Garg Saweta S Shiekh Bilal Ahmad BA Singh Nirmal N Singh Palwinder P Bhatti Rajbir R

ACS omega 20200618 25

The current investigation was aimed at in vivo MAOA inhibitory activity of coumarins angelicin, bergapten, and scopoletin isolated from the roots of Angelica archangelica. The isolated compounds were screened for MAOA (pdb ID 2Z5y) binding through molecular docking studies. The molecular docking results displayed that bergapten has a maximum affinity for MAOA, followed by angelicin and scopoletin. In silico prediction of physicochemical param ...[more]

PMID: 32637779

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Project description:BACKGROUND:Angelica shikokiana is a Japanese medicinal herb that is included among food and drug preparations protecting against cancer; however, there is no previous report about the cytotoxicity of A. shikokiana or its bioactive compounds. OBJECTIVE:This study was designed to investigate the cytotoxic activities of A. shikokiana methanol extract (AME) and its isolated compounds and to identify the molecular mechanisms of the cytotoxicity. MATERIALS AND METHODS:Cytotoxicity and selectivity was investigated by measuring the IC50 values on five cancer cell lines; human hepatocellular carcinoma, rhabdomyosarcoma (RD), colorectal carcinoma, human epithelioma and human breast adenocarcinoma and one normal cell line; human lung fibroblasts. The effects on tubulin polymerization and histone deacetylase 8 (HDAC8), were examined to determine the mechanism of cytotoxicity. Docking study was designed to examine the binding affinity to the target molecules. RESULTS:Methanol extract and some of its isolated coumarins and flavonoids showed potent, selective cytotoxicity against cancer cell lines. AME and all isolated compounds inhibited tubulin polymerization. Angelicin and kaempferol-3-O-rutinoside were the most active compounds. Phenolic compounds and furanocoumarins showed binding affinity to colchicine binding site rather than the vinblastine binding site of tubulin microtubules. On the other side, quercetin, kaempferol, luteolin, chlorogenic acid, and methyl chlorogenate exhibited the strongest activity against HDAC8 and the highest affinity to trichostatin A binding site. CONCLUSION:These findings provide the first scientific evidence of the cytotoxicity of AME through inhibition of tubulin polymerization and HDAC8 activity through its coumarin and flavonoid content. SUMMARY:The present study provides for the first time a clue for the cytotoxic activities of the AME. Our results indicate that the cytotoxic activities are partially related to the ability of AME to inhibit tubulin polymerization and HDAC8 activity. Isolated compounds; Angelicin and kaempferol-3-O-rutinoside showed the strongest inhibition of tubulin polymerization through binding to colchicine binding domain of tubulin microtubules. Phenolic compounds; quercetin, luteolin, kaempferol, chlorogenic acid and methyl chlorogenate exhibited a strong inhibition of HDAC8 through binding to TSA binding site. This, however, further detailed pharmacological and in vivo studies should be the next step in evaluating the cytotoxic activities of AME and its active compounds that are currently ongoing. Abbreviations used: AME: Methanol extract of the aerial part of A. shikokiana, HDACs: Histone deacetylases,HDAC8: Histone deacetylase 8.

Project description:BackgroundsLeucas cephalotes is a common ethnomedicinal plant widely used by traditional healers for the treatment of Malaria and other types of fever. Oleanolic acid and its derivatives have been reported for various types of pharmacological activities, such as anti-inflammatory, antioxidant, anticancer, hepatoprotective, anti-HIV and anti-HCV activity.MethodsL.cephalotes plant extracts were prepared by supercritical fluid extraction (SFE) method and oleanolic acid was isolated by preparatory thin-layer chromatography. The compound was identified and characterize by using ultraviolet-visible spectroscopy (UV-VIS), Fourier transform infra-Red spectroscopy (FT-IR) and high-performance thin-layer chromatography (HPTLC). The structure of the compound was elucidated by proton nuclear magnetic resonance (1HNMR) and carbon nuclear magnetic resonance (1CNMR) and the purity checked by differential scanning calorimetry (DSC). The MTT assay was used to determine the toxicity of plant extract and oleanolic acid using a microplate reader at 595 nm. The anti-dengue activity of plant extract and oleanolic acid was tested in vitro and in silico using real-time RT-PCR.ResultsThe optimum yield of the extract was obtained at 40 °C temperature and 15Mpa pressure. The maximum non-toxic dose (MNTD) of plant extract and oleanolic acid were found as 46.87 μg/ml and 93.75 μg/ml, respectively in C6/36 cell lines. UV spectrophotometer curve of the isolated compound was overlapped with standard oleanolic acid at 232 nm. Superimposed FT-IR structure of the isolated compound was indicated the same spectra at 3433, 2939, 2871, 1690, 1500,1463, 1387, 1250, 1209, 1137 and 656 position as per marker compound. HPTLC analysis showed the retention factor of L. cephalotes extract was 0.19 + 0.06 as similar to the standard oleanolic acid chromatogram. The NMR structure of the isolated compound was identified as similar to the marker oleanolic acid structure. DSC analysis revealed the purity of isolated oleanolic acid was 98.27% with a melting point of 311.16 °C. Real-time RT PCR results revealed that L. cephalotes supercritical extract and isolated oleanolic acid showed 100 and 99.17% inhibition against the dengue - 2 virus when treated with MNTD value of plant extract (46.87 μg/ml) and the test compound (93.75 μg/ml), respectively. The molecular study demonstrated the binding energy of oleanolic acid with NS1and NS5 (non-structural protein) were - 9.42 & -8.32Kcal/mol, respectively.ConclusionsThe SFE extract L. cephalotes and its active compound, oleanolic acid inhibiting the activity of dengue-2 serotype in the in vitro and in silico assays. Thus, the L.cephalotes plant could be an excellent source for drug design for the treatment of dengue infection.

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In Silico Studies and In Vivo MAOA Inhibitory Activity of Coumarins Isolated from Angelica archangelica Extract: An Approach toward Antidepressant Activity.

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<i>In</i> <i>Silico</i> Studies and <i>In Vivo</i> MAO<sub>A</sub> Inhibitory Activity of Coumarins Isolated from <i>Angelica archangelica</i> Extract: An Approach toward Antidepressant Activity.

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